PCYOX1 (prenylcysteine oxidase 1) is a FAD-dependent enzyme that catalyzes the final degradation step of prenylated proteins by cleaving the thioether bond of free prenylcysteines, such as farnesylcysteine and geranylgeranylcysteine, releasing cysteine, an aldehyde, and hydrogen peroxide 1. The enzyme is primarily expressed in liver, gastrointestinal tract, kidney, male reproductive tissue, and muscle, and is transported within lipoproteins, particularly LDLs and VLDLs 1. PCYOX1 functions as a pro-oxidant enzyme with a structured mechanism involving rapid flavin reduction-reoxidation cycles, with product release limiting overall reaction rate 2. Disease relevance spans atherosclerosis, where PCYOX1 promotes atherogenesis through increased hydrogen peroxide production and oxidative stress, with PCYOX1 deficiency retarding atheroprogression and reducing lesion vulnerability in Apoe-/- mice 3. Emerging evidence suggests protective associations with lung adenocarcinoma risk 4 and roles in fibromyalgia pathophysiology 5. Notably, PCYOX1-containing VLDLs induce neutrophil extracellular trap formation in lupus-like disease contexts 6, and elevated exosomal PCYOX1 predicts insulin resistance and hepatic steatosis in childhood following small-for-gestational-age birth 7. These findings establish PCYOX1 as an emerging therapeutic target in cardiovascular and metabolic diseases.